Author Archives: David

Therapeutic potential of cannabis for surgical wound healing in rats

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“This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds.

An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis.

The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05).

To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.”

https://pubmed.ncbi.nlm.nih.gov/39296630/

http://vetmed.agriculturejournals.cz/artkey/vet-202408-0002_therapeutic-potential-of-cannabis-for-surgical-wound-healing-in-rats.php

Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome

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“Brain aging is associated with cognitive decline, reduced synaptic plasticity, and altered metabolism. The activity of mechanistic target of rapamycin (mTOR) has a major impact on aging by regulating cellular metabolism. Although reduced mTOR signaling has a general antiaging effect, it can negatively affect the aging brain by reducing synaptogenesis and thus cognitive functions. Increased mTOR activity facilitates aging and is responsible for the amnestic effect of the cannabinoid receptor 1 agonist Δ9-tetrahydrocannabinol (THC) in higher doses.

Long-term low-dose Δ9-THC had an antiaging effect on the brain by restoring cognitive abilities and synapse densities in old mice.

Whether changes in mTOR signaling and metabolome are associated with its positive effects on the aging brain is an open question. Here, we show that Δ9-THC treatment has a tissue-dependent and dual effect on mTOR signaling and the metabolome.

In the brain, Δ9-THC treatment induced a transient increase in mTOR activity and in the levels of amino acids and metabolites involved in energy production, followed by an increased synthesis of synaptic proteins. Unexpectedly, we found a similar reduction in the mTOR activity in adipose tissue and in the level of amino acids and carbohydrate metabolites in blood plasma as in animals on a low-calorie diet.

Thus, long-term Δ9-THC treatment first increases the level of energy and synaptic protein production in the brain, followed by a reduction in mTOR activity and metabolic processes in the periphery.

Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective antiaging and pro-cognitive medication.”

https://pubmed.ncbi.nlm.nih.gov/39296258/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00002

The endocannabinoid system in appetite regulation and treatment of obesity

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“The endocannabinoid system (ECS) is a complex cell-signaling system that is responsible for maintaining homeostasis by modulating various regulatory reactions in response to internal and environmental changes. The influence of ECS on appetite regulation has been a subject of much recent research, however, the full extent of its impact remains unknown.

Current evidence links human obesity to ECS activation, increased endocannabinoid levels in both central and peripheral tissues, along with cannabinoid receptor type 1 (CBR1) up-regulation. These findings imply the potential pharmacological use of the ECS in the treatment of obesity.

Here, we present various pathophysiological processes in obesity involving the ECS, highlighting different pharmacological options for modulating endocannabinoid activity to treat obesity. However, the potential of those pharmacological possibilities remains under investigation and requires further research.”

https://pubmed.ncbi.nlm.nih.gov/39292202/

Cannabidiol modulation of immune cell function: in vitro insights and therapeutic implications for atopic dermatitis

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“Introduction: Cannabidiol (CBD) exhibits neuroprotective, anti-inflammatory, and immunomodulatory properties, making it a promising candidate for addressing inflammatory skin disorders like atopic dermatitis.

Aim: This study aimed to (i) investigate CBD’s impact on lymphocyte proliferation and lymphocyte viability; (ii) assess in vitro cytotoxicity U937 cells (a human promonocytic cell line) of CBD/cytotoxicity of CBD on U937 cells; (iii) provide insights into CBD immunomodulatory potential, and (iv) evaluate suitability of CBD for treating inflammatory skin conditions.

Material and methods: To this aim PBMCs from healthy donors were cultured with mitogen and two different CBD doses (0.1 and 1 mg/ml), assessing B and T cell proliferation through flow cytometry. CBD inhibited mitogen-induced lymphocyte proliferation, reducing the percentage of proliferating T and B cells. Notably, both CBD doses did not exhibit cytotoxicity on lymphocytes as revealed by viability assessment. We also analysed the effect of CBD on U937 cells using an optical microscopy approach. Interestingly, the higher dose of CBD exerted a cytotoxic effect on U937 cells, while the lower dose was well tolerated.

Results: We analysed the effect of an adjuvant treatment for atopic dermatitis with a CBD-containing cleansing cream in reducing itch. Notably, the treatment with the CBD-containing cleansing cream significantly reduced itch in patients suffering from atopic dermatitis.

Conclusions: These findings affirm CBD’s immunomodulatory characteristics, emphasizing its potential therapeutic application in inflammatory skin disorders.”

https://pubmed.ncbi.nlm.nih.gov/39290893/

https://www.termedia.pl/Cannabidiol-modulation-of-immune-cell-function-in-vitro-insights-and-therapeutic-implications-for-atopic-dermatitis,7,54606,0,1.html

Measuring the Impact of Medical Cannabis Law Adoption on Employer-Sponsored Health Insurance Costs: A Difference-in-Difference Analysis, 2003-2022

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“Introduction: Recent studies suggest that medical cannabis laws may contribute to a relative reduction in health insurance costs within the individual health insurance markets at the state level. We investigated the effects of adopting a medical cannabis law on the cost of employer-sponsored health insurance in the United States.

Methods: We analyzed state-level data from the Medical Expenditure Panel Survey-Insurance Component (MEPS-IC) Private Sector spanning from 2003 to 2022. The outcomes included log-transformed average total premium costs per employee for single, employee-plus-one, and family coverage plans. We utilized the Sun and Abraham (J Econometr 225(2):175-199, 2021) difference-in-difference (DiD) method, looking at the overall DiD and event-study DiD. Models were adjusted for various state-level demographics and dichotomous policy variables, including whether a state later adopted recreational cannabis, as well as time and unit fixed effects and population weights.

Results: For states that adopted a medical cannabis law, there was a significant decrease in the log average total premium per employee for single (-0.034, standard error [SE] 0.009 (-$238)) and employee-plus-one (-0.025, SE 0.009 (-$348)) coverage plans per year considering the first 10 years of policy change compared with states without such laws. Looking at the last 5 years of policy change, we saw increases in effect size and statistical significance. In-time placebo testing suggested model robustness. Under a hypothetical scenario where all 50 states adopted medical cannabis in 2022, we estimated that employers and employees could collectively save billions on healthcare coverage, potentially reducing healthcare expenditure’s contribution to GDP by 0.65% in 2022.

Conclusion: Adoption of a medical cannabis law may contribute to decreases in healthcare costs. This phenomenon is likely a secondary effect and suggests positive externalities outside of medical cannabis patients.”

https://pubmed.ncbi.nlm.nih.gov/39287774/

Phytochemistry and pharmacological activities of Cannabis sativa fruit (Cannabis Fructus)

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“Cannabis sativa fruit (Cannabis Fructus) refers to the dried and ripe fruit of Cannabis sativa L. It is widely distributed in the northeast, North, and South China. It has medicinal, ecological, and economic values.

This study aimed to review the chemical constituents and pharmacological activities of Cannabis Fructus, providing a reference for further exploration of Cannabis Fructus. Comprehensive information on Cannabis Fructus was collected via electronic searches (e.g., Google Scholar, PubMed, Sci Finder, and Web of Science) and from books on phytochemistry.

Cannabis Fructus contains various compounds such as phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins, and polysaccharides. Its active ingredients exhibit anti-inflammatory, anti-oxidant, anti-bacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotective, lipoid-regulating, hepatoprotective, and immunomodulatory properties.”

https://pubmed.ncbi.nlm.nih.gov/39278423/

“Highlights

  • •Cannabis Fructus is the dried and ripe fruit of Cannabis sativa L, it has a long history of medicinal and edible use.
  • •Compounds in Cannabis Fructus include phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins and polysaccharides.
  • •Cannabis Fructus and its active ingredients have anti-inflammatory, antioxidant, antibacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotection, lipoid-regulating and liver-protecting activities and immunomodulatory activities.
  • •Cannabis Fructus can be used as the main raw material in the development of food, medicine, cosmetics, health products industry.”

https://www.sciencedirect.com/science/article/abs/pii/S0367326X24003976?via%3Dihub

Disease-Modifying Symptomatic Treatment (DMST) Potential of Cannabinoids in Patients with Multiple Sclerosis

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“With the recent introduction of a number of highly effective disease-modifying treatments (DMTs) and the resulting almost complete prevention of acute relapses in many patients with multiple sclerosis (MS), the interest of MS clinicians has gradually shifted from relapse prevention to counteraction of disease progression and the treatment of residual symptoms.

Targeting the cannabinoid system with nabiximols is an approved and effective strategy for the treatment of spasticity secondary to MS.

Recently, the concept of spasticity plus syndrome (SPS) was introduced to account for the evidence that spasticity often appears in MS patients in clusters with other symptoms (such as pain, bladder dysfunction, sleep, and mood disorders), where cannabinoids can also be effective due to their broader action on many immune and neuronal functions. Interestingly, outside these symptomatic benefits, extensive pre-clinical and clinical research indicated how the modulation of the cannabinoid system results in significant anti-inflammatory and neuroprotective effects, all potentially relevant for MS disease control.

This evidence makes nabiximols a potential disease modifying symptomatic treatment (DMST), a concept introduced in an attempt to overcome the often artificial distinction between DMTs and symptomatic therapies (STs).”

https://pubmed.ncbi.nlm.nih.gov/39279696/

https://www.eurekaselect.com/article/143047

Effectiveness of Cannabinoids Treatment in Pain Management and Other Fibromyalgia-Associated Symptoms: A Case Series

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“Pharmacological therapies for FM are still ineffective in many patients, involving adverse effects that hinder their long-term use.

We aimed to assess the effectiveness of cannabinoids (Tilray Dried Flower THC18) in the management of chronic pain and other FM-associated symptoms according to patient-reported outcomes, in a series of three FM patients. 

We observed improvements after one and three months of cannabinoids treatment in Brief Pain Inventory (BPI), Visual Analogue Scale (VAS), Insomnia Severity Index (ISI), SF-36 Health Survey, and Fibromyalgia Impact Questionnaire (FIQ) allowing pain relief, and improvements in sleep quality, performance of daily life activities, and quality of life.

In conclusion, although more studies are needed, in our series of FM patients, cannabinoids treatment showed promising results in the management of chronic pain and other FM-associated symptoms, improving the quality of life of these patients.”

https://www.heraldopenaccess.us/openaccess/effectiveness-of-cannabinoids-treatment-in-pain-management-and-other-fibromyalgia-associated-symptoms-a-case-series

Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes

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“Cannabinol (CBN) is a secondary metabolite of cannabis whose beneficial activity on inflammatory diseases of human skin has attracted increasing attention. Here, we sought to investigate the possible modulation by CBN of the major elements of the endocannabinoid system (ECS), in both normal and lipopolysaccharide-inflamed human keratinocytes (HaCaT cells).

CBN was found to increase the expression of cannabinoid receptor 1 (CB1) at gene level and that of vanilloid receptor 1 (TRPV1) at protein level, as well as their functional activity. In addition, CBN modulated the metabolism of anandamide (AEA) and 2-arachidonoylglicerol (2-AG), by increasing the activities of N-acyl phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH)-the biosynthetic and degradative enzyme of AEA-and that of monoacylglycerol lipase (MAGL), the hydrolytic enzyme of 2-AG.

CBN also affected keratinocyte inflammation by reducing the release of pro-inflammatory interleukin (IL)-8, IL-12, and IL-31 and increasing the release of anti-inflammatory IL-10. Of note, the release of IL-31 was mediated by TRPV1. Finally, the mitogen-activated protein kinases (MAPK) signaling pathway was investigated in inflamed keratinocytes, demonstrating a specific modulation of glycogen synthase kinase 3β (GSK3β) upon treatment with CBN, in the presence or not of distinct ECS-directed drugs.

Overall, these results demonstrate that CBN modulates distinct ECS elements and exerts anti-inflammatory effects-remarkably via TRPV1-in human keratinocytes, thus holding potential for both therapeutic and cosmetic purposes.”

https://pubmed.ncbi.nlm.nih.gov/39275884/

“Taken together, our data suggest that CBN may hold true therapeutic potential to treat different human skin diseases. Such a biological activity of CBN occurs through engagement of selected elements of the endocannabinoid system—in particular TRPV1—a finding that paves the way to the development of distinct formulations of cannabis extracts for selected therapeutic applications.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.2122

Cannabinoids in the Inflamed Synovium Can Be a Target for the Treatment of Rheumatic Diseases

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“The management of rheumatic diseases has noticeably changed in recent years with the development of targeted therapeutic agents, namely, biological disease-modifying antirheumatic drugs. Identifying essential signaling pathways and factors crucial for the development and progression of these diseases remains a significant challenge.

Therapy could be used to delay the onset or reduce harm. The endocannabinoid system’s presence within the synovium can be identified as a suggested target for therapeutic interventions due to its role in modulating pain, inflammation, and joint metabolism.

This review brings together the most pertinent information concerning the actions of the endocannabinoid system present in inflamed synovial tissue and its interaction with phytocannabinoids and synthetic cannabinoids, which can be used from a therapeutic perspective to minimize the inflammatory and pain processes typical of osteoarthritis and rheumatoid arthritis.”

https://pubmed.ncbi.nlm.nih.gov/39273304/

https://www.mdpi.com/1422-0067/25/17/9356